The following is a summary of “Effects of Bardoxolone Methyl in Alport Syndrome” published in the December 2022 issue of Nephrology by  A. Warady et, al.

Kidney failure is a hallmark of the genetic condition known as Alport syndrome. In this study, researchers intended to determine if bardoxolone methyl was safe and effective for patients with Alport syndrome. Patients (12–70 years old) with Alport syndrome and epidermal growth factor receptor(eGFR)  (glomerular filtration rate) of 30–90 ml/min per 1.73 m2 were randomly assigned to receive either bardoxolone methyl (n=77) or a placebo (n=80). Baseline eGFR and eGFR at weeks 48 and 100 were the primary efficacy end objectives. 

The primary, secondary efficacy end measure was the percentage change from baseline in eGFR at weeks 52 and 104, following an intentional 4-week treatment break. Vital signs, 12-lead electrocardiograms(ECGs), laboratory measures (including, but not limited to, aminotransferases, urinary albumin-creatinine ratio, magnesium, and B-type natriuretic peptide), and body weight were tracked to look for adverse events and evaluate changes from baseline. At 48 weeks (between-group difference: 9.2 [97.5% CI, 5.1 to 13.4; P<0.001]) and 100 weeks (between-group difference: 7.4 [95% CI, 3.1 to 11.7; P=0.0008] ml/min per 1.73 m2), patients randomized to bardoxolone methyl had preserved eGFR compared to placebo. Mean differences in eGFR between treatment periods were 5.4 (97.5% CI, 1.8 to 9.1; P<0.001) and 4.4 (95% CI, 0.7 to 8.1; P=0.02) ml/min per 1.73 m2 at 52 and 104 weeks, respectively. This difference at week 104 was not statistically significant (1.5 [95% CI, 1.9 to 4.9] ml/min per 1.73 m2) in a post hoc analysis without imputation of missing eGFR data. 

Patients assigned to receive bardoxolone methyl had a higher rate of treatment termination; most of these discontinuations were due to meeting protocol-specified criteria for elevations in serum transaminases. Patients who were randomly assigned to receive the placebo had a higher incidence of serious adverse events. Kidney failure struck 3 patients in both treatment groups. Bardoxolone methyl therapy preserved eGFR compared to placebo after 2 years in adolescents and adults with Alport syndrome who were getting routine care; off-treatment findings utilizing all available data were not substantially different.